91: Contralateral Sensitisation in Chonic Pain in Mice

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Electrophysiology, Assessment and Measurement of Pain/Nociception, Neuroanatomical circuit analysis

Background and Aims: Normally, as a posttraumatic reaction, spinal fields enlarge mostly ipsilateral to a distal injury and many of these enlarged fields return to normal size during healing. However, in some cases spinal changes spread to the contralateral side and field sizes enlarge more and cluster in the cord as early as in the posttraumatic phase. In these cases, fields shrink on the ipsilateral side long after trauma. In a compensatory attempt, the body might try to minimize the impact of pathologically altered neurons by minimizing their receptive fields.
Neuroinflammation intensifies with age, and microglial activation spreads contralaterally in tibia fractured mice.

Methods: WDR neurons in the murine spinal dorsal horn were recorded. Receptive fields and activity upon mechanically stimulating the receptive field were measured for each recorded neuron. Spinal maps were created for each animal, young and aged healthy mice, and young and aged tibia fractured mice showing receptive field size and pressure response of every neuron in relation to its spinal location. The typical posttraumatic enlargement of receptive fields surrounded the whole paw in a glove shape. Receptive field size of a cell was correlated with its response to the peripheral stimulus on either side of the spinal cord.

Results: Young mice differ from aged mice in their phenotype and their spinal WDR neuronal properties.
Young mice (6 weeks) developed a posttraumatic phenotype after fracture + casting that subsided within weeks. Aged mice (12 months) also developed a posttraumatic phenotype after fracture + casting but maintained a chronic phenotype. WDR responses to pressure stimuli were enhanced most often in cells with large receptive fields in the acute phase and small receptive fields in the chronic stage. Neurons with large field sizes occured in all groups post fracture but neurons with small fields were observed only in mice that developed a chronic phenotype.

Conclusions: Spinal neuronal changes can predict the outcome after bone fracture
in the early posttraumatic phase.

References: Hirsch et al., Pain, 2024
Hirsch et al., J. Pain, 2025
Brahadeeswaran et al., Mol. Neurobiol., 2022

Presenting Author: Silke Hirsch
Submitting Author: Silke Hirsch

Senior Author: Frank Birklein

IASP 2026 Global Year theme of Neuropathic Pain: No

• Peter Drummond: Prof. - Department of Psychology, Murdoch University Perth, Australia
• Frank Birklein: Prof. - Department of Neurology, Unimedizin Mainz, Germany